CLCF1

Chr 11q13.2

cardiotrophin like cytokine factor 1

Aliases:: NNT1, BSF3, CLC, NR6, CISS2
MANE:: ENST00000312438.8

OMIM: 607672 ↗NCBI: 23529 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

CLCF1 · Q9UBD9

v62025-08-01

Predicted Aligned Error matrix for CLCF1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

81.6/ 100

Confident

225 residues

Confidence breakdown

Very high(≥ 90)57%
Confident(70–90)13%
Low(50–70)19%
Very low(< 50)11%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Moderate Evidence (Amber)

Arthrogryposis
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

cold-induced sweating syndrome
0.60
Crisponi syndrome
0.37
smoking initiation
0.22
dislocation
0.18
hepatocellular carcinoma
0.09
glioma
0.09
central nervous system cancer
0.09
glioblastoma
0.09
familial long QT syndrome
0.08
Romano-Ward syndrome
0.08

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Cardiotrophin-like cytokine factor 1

Functions as a cytokine, either alone or by forming a stable complex with soluble CRLF1 or CNTFR (PubMed:10448081, PubMed:10500198, PubMed:10966616, PubMed:11285233, PubMed:11294841). Binds to CNTFR complex (CNTFR, IL6ST/gp130, LIFR) or can signal via trans-signaling using soluble CNTFR subunits (PubMed:10966616, PubMed:11285233, PubMed:11294841). Mechanistically, ligand binding to CNTFR, induces dimerization of the IL6ST/gp130 and LIFR, which activates JAK tyrosine kinases (JAK1 or JAK2 and to lesser extent TYK2) bound to their intracellular domains (PubMed:11294841, PubMed:16782820). These kinases subsequently phosphorylate IL6ST/gp130 and LIFR (PubMed:11294841). The tyrosine phosphorylated signaling receptors serve in turn as docking sites for recruitment and activation of signal transducer and activators of transcription (STAT3 and to lesser extent STAT1) (PubMed:10448081, PubMed:10500198, PubMed:10966616, PubMed:11285233, PubMed:11294841, PubMed:16782820). Moreover, CLCF1/CLF heterodimer induces tyrosine phosphorylation of PTPN11, that associates with IL6ST/gp130-LIFR, which in turn recruits PIK3 protein kinase followed by AKT protein phosphorylation (PubMed:11294841). Participates in the survival of embryonic motor neurons (PubMed:10500198, PubMed:10966616). Also stimulates B-cells (By similarity)